Influence of Caspase-9 polymorphisms on the development of Chronic Myeloid Leukemia- A case-control study.
Apoptosis
Caspase 9 polymorphisms
Chronic Myeloid Leukemia
Haplotype
RFLP
Journal
Gene
ISSN: 1879-0038
Titre abrégé: Gene
Pays: Netherlands
ID NLM: 7706761
Informations de publication
Date de publication:
2019
2019
Historique:
received:
17
07
2018
accepted:
30
11
2018
entrez:
17
9
2021
pubmed:
1
1
2019
medline:
1
1
2019
Statut:
ppublish
Résumé
Chronic Myeloid Leukemia (CML) is a myeloproliferative disorder, characterized by the overproduction of myeloid cells in all stages of maturation. It is usually defined by three sequential stages (Chronic, Accelerated and Blast-crisis) where the transition from chronic to accelerated to blast phases is presumed to occur due to secondary genetic changes, viz. accumulation of mutations, activation of downstream pathways and failure of apoptosis. Caspase 9 is the initiator caspase involved in mitochondrial-mediated apoptotic pathway. Polymorphisms in the promoter (-1263 A>G, -712C>T, -293 del) and coding (Ex5 +32G>A) regions of CASP9 gene are found to influence the expression levels by either impairing the activation or loss of expression of CASP9 or insufficient formation of apoptosome. The present case-control study was carried out on 999 individuals, comprised of 485CML cases reported at Nizams Institute of Medical Sciences (NIMS), Hyderabad and 514 age and gender-matched healthy individuals from local population. DNA was isolated by non-enzymatic/salting-out method and was genotyped using RFLP technique. It was observed that the presence of G allele of CASP9 -1263A>G polymorphism enhanced the risk for CML while CASP9 -712C>T and CASP9 -293del SNPs conferred protection against development of CML. Haplotype analysis of promoter and exonic polymorphisms had revealed increased risk associated with two haplotypes G_C_del (+)_G (OR-1.61, 95% CI-0.97-2.65, p-0.06#) and G_C_del (-)_G (OR-2.09, 95% CI-0.94-4.66, p-0.07#) suggesting the role of G allele of CASP9 -1263A>G in conferring risk independent of other SNPs. Pairwise LD analysis performed for all the four SNPs revealed the presence of LD among the SNPs. The results of the present study therefore concludes the role of CASP9 -1263A>G polymorphism in increasing the risk for the development and progression while CASP9 -712C>T and CASP9 -293del SNPs conferred protection and CASP9 Ex5 +32G>A was involved in conferring resistance which could be in combination with other SNPs or factors affecting them.
Identifiants
pubmed: 34530993
pii: S2590-1583(18)30002-0
doi: 10.1016/j.gene.2018.100002
pmc: PMC7286081
pii:
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
100002Informations de copyright
Copyright © 2018 The Author(s). Published by Elsevier B.V. All rights reserved.
Références
Pancreas. 2010 Oct;39(7):976-80
pubmed: 20357690
BJU Int. 2011 Feb;107(3):471-6
pubmed: 20804486
Exp Ther Med. 2013 Jan;5(1):175-180
pubmed: 23251262
Cancer Genet. 2012 Oct;205(10):508-12
pubmed: 22981751
Tumour Biol. 2014 Sep;35(9):8813-22
pubmed: 24879622
Med Oncol. 2012 Dec;29(4):2445-51
pubmed: 22120515
Hum Mol Genet. 2006 Jun 15;15(12):1963-71
pubmed: 16687442
Genes Immun. 2001 Apr;2(2):117-8
pubmed: 11393657
Hematol Oncol. 2008 Sep;26(3):148-51
pubmed: 18381704
Blood. 1994 Apr 15;83(8):2038-44
pubmed: 8161775
PLoS One. 2012;7(5):e37443
pubmed: 22616010
Gastric Cancer. 2011 Oct;14(4):317-21
pubmed: 21461653
Mutat Res. 2009 Nov-Dec;680(1-2):56-63
pubmed: 19815090
J Thorac Oncol. 2010 Aug;5(8):1152-8
pubmed: 20661084
Mamm Genome. 1999 Jul;10(7):757-60
pubmed: 10384055
Biochim Biophys Acta. 1998 Aug 10;1366(1-2):139-49
pubmed: 9714780
Tumour Biol. 2016 Apr;37(4):5475-84
pubmed: 26563376
Nucleic Acids Res. 1991 Oct 11;19(19):5444
pubmed: 1681511
Carcinogenesis. 2007 Apr;28(4):823-7
pubmed: 17071630